Obesity Pathophysiology and Treatment

November 14, 2019

Obesity is defined as having
an excess of body fat, and we focus on having
too much body fat because that is harmful. Body fatness can be measured
directly or can be estimated. Body fat is estimated by the body mass index, BMI measure. This is body weight in pounds
or kilograms divided by height in inches or centimeters. The height value
in the denominator is squared so that tallness has a lowering
effect on the measure. There are some websites that
will calculate the BMI measure so it doesn’t
have to be done manually. Data has shown that
the larger the BMI, the more risk for obesity
related disease such as type II diabetes
and heart disease. The BMI calculation uses just
body weight and height to estimate body fatness. It is therefore not
a direct measure of body fat. For this reason, BMI can be
inaccurate if the body weight of the individual
is really high due to muscle. For example, many athletes have
excess weight because they have a lot of body muscle rather
than having a lot of body fat. The BMI measure classifies that
such individuals are obese, but this is inaccurate. Also, comparisons between women
and men at the same BMI would indicate that they
have similar body fat, but actually women tend to carry
more body fat than men. Again, older and younger people
can be shown to have the same BMI, but usually
the older person has more body fat. This indicates that using BMI
may not be sufficient when estimating a person’s
body fat and, therefore, their risk for developing
obesity related disease. The most accurate measurement
for measuring body fat, or the gold standard measure, is called air displacement plethysmography. It measures body fat using
body volume and body weight to calculate body density. Since fat is less dense
than other body tissues, like muscle and bone, knowing
a person’s body density can be used to measure
body fatness. The air displacement method
replaces underwater weighing, which works the same way, but is much more challenging
to measure. Obesity is defined as having a body fat level greater than 25% if you are a man, and greater than 35%
if you are a woman. Other instruments can measure
the total fat in the body, including:
bioelectrical impedance, magnetic resonance imaging,
or dual x-ray absorptiometry. Unfortunately, many
of the instruments used to measure body fat directly
are very expensive and are only used
in the research setting. Another way to assess obesity
is to measure body fatness in particular regions
in the body. Measuring fat
in the abdominal region is particularly informative because having too much fat in the abdomen is detrimental. To do this, we can measure waist
circumference or the height of the abdominal area. These two measures are cheap
and easy to do in the clinic or other settings and can provide important information about a person’s risk
of disease from obesity. So we just talked about how
we can estimate obesity, but how does obesity
actually occur? Data shows that obesity
is a result of an imbalance of energy intake
and energy expenditure. When we ingest foods and drink,
we take in energy in the form of calories in proteins,
fats, and carbohydrates. We need that energy
for organs to function, and this is called
basal metabolism. We also need energy
to digest our food, and this is called
dietary thermogenesis. We also need energy when we are- when our muscles are active, such as standing,
walking, or exercise. If we take in too much energy
and don’t use it for these functions, the excess
energy is stored as fat. This was advantageous
when we had a scarcity of food. Fat stores could be relied upon for energy during times
of starvation. However, currently,
cheap and excess food is readily available and people get very little exercise, especially in developed
countries around the world, and the result of this
is obesity. There are debates about whether
energy imbalance is the only root to obesity. Some researchers have hypothesized that obesity is due to viral infections,
environmental pollutants, sugar consumption,
better control of the temperature
of our environment, and other factors,
but evidence for these hypotheses
is not yet convincing. There are many diseases
that have been shown to be a consequence of obesity. The relationship between obesity
and type II diabetes is the most studied
and understood. However, obesity
can negatively impact most of the physiological systems in the body including the cardiovascular, causing heart disease and stroke;
the endocrine, causing diabetes; the reproductive system, causing menstrual
disorders and infertility; the musculoskeletal sk-system,
causing osteoarthritis and gout; the respiratory system,
causing sleep apnea and asthma; and the gastrointestinal system,
causing fatty liver and reflux disease. Obesity has also been associated
with various cancers including breast, liver, pancreas, and colorectal. Psychological health can be also
impacted by obesity including depression, negative
self-esteem, and social stigmatization. Society has negative attitudes
about people who are obese that can affect their ability
to obtain employment, education, and healthcare. There are debates about whether
obesity is bad for our health, as some of the data suggests. However, when we look at changes
in health in people who were obese and have
experienced weight loss, we find strong evidence
for the causal link between obesity and disease. Weight loss causes a decrease
in risk of many diseases including diabetes,
heart disease, cancer, and even depression, as well as improved quality of life. This supports the claim that
obesity is bad for health. The reason that excess body
fat leads to disease is under investigation. One major finding,
realized about 20 years ago, is that adipose tissue produces a number of hormones and other molecules that are involved in the immune system, called cytokines. This slide shows many
of the molecules made by adipose tissue. When adipose tissue
is in excess, the levels of harmful hormones
and cytokines are increased and the levels of beneficial
hormones are decreased. The normal function of cytokines
is to attack foreign invaders in the body, but when they’re
elevated in obese states, they attack the body itself. Higher than normal levels
of cytokines such as leptin, interleukin-6, tumor
necrosis factor alpha, and lower than normal levels
of factors such as adiponectin can influence processes such as
oxidative stress, inflammation, and cell growth in ways
that can be detrimental. This slide shows visually
the impact of adipose tissue in the abdominal area. Excess adipose tissue
accumulated in the intraabdominal area, especially around the liver, the stomach, and the pancreas, is more prone to producing harmful cytokines
compared to adipose tissue that’s located in the hips
and thighs. This is why having an apple
shape due to central adiposity is more risky for heart disease,
diabetes, and cancer compared to having a pear shape. For women, their risk increases
if waist circumference is greater than 88 centimeters, or 35 inches. For men, their risk increases if
waist circumference is greater than 102 centimeters, or 40
inches according to guidelines from the National Heart,
Lung, and Blood Institute. Because of all the data showing
the harmful effects of excess adipose tissue, obesity was finally classified as a disease in June 2013. This enables doctors to provide
obesity treatment to patients and specifies that treatment
for this disease should be covered
under insurance. So, now that we know we
should be treating obesity, what are the approaches that
can be used to treat obesity? So, managing obesity by weight
loss is a good way to reduce the risk of obesity
related disease. The three approaches
used to treat obesity are lifestyle modification, pharmacology, and bariatric surgery,
and the recommendations for each depend on the severity
of obesity. The guidelines for selecting
each treatment approach were updated in 2013 by experts in the American College
of Cardiology, the American Heart Association, and the Obesity Society for the U.S. population. For all categories of weight-
of overweight and obesity, lifestyle or behavior
modification strategies are recommended. Lifestyle modification includes
changing an individual’s dietary or activity behavior to reduce
calories and increase exercise. A variety of dietary
and physical activity approaches have been shown to be effective
in producing about a 5% reduction
in body weight in overweight and obese individuals. Although a 5% reduction in body
weight can be as small as only 10 pounds
in some individuals, there are health benefits associated with that including
a lower blood sugar level and a lower blood
pressure level. Examples of dietary approaches
to induce weight loss are the low-fat diet,
the low-carbohydrate diet, or the Mediterranean diet. A research study that was
recently done by Shai and others compared the benefits
of these three different dietary approaches. Their findings showed that all
three diets were effective in the short term. This is good because years
of study have shown that a one size fits all approach does not work, and we may need
to tailor strategies to individual patients
for better weight loss results. As the slide shows, after
about six months on the diets, the participants gained some
of their weight back. This is a common finding
as maintenance of weight loss is a problem for many people
and they regain the lost weight over the long term. The study by Shai and others
showed the benefits of weight loss in people who used either a low-fat diet, a Mediterranean-style diet,
or a low-carbohydrate diet. In the left panel, you can see
the rise in HDL cholesterol, which is good, because
that’s the good cholesterol. In the right panel, you can
see the drop in triglycerides, and both of these changes
are beneficial for lowering heart disease. Pharmacology is the second
approach that we can use to treat individuals
for obesity. Remember that pharmacology
can be used in individuals who are overweight and have health complications such as diabetes
or high blood pressure, or individuals who are obese. Although there is a tremendous
number of drugs that claim to treat obesity, and this is
a billion dollar industry, there are few drugs that have
actually been proven to be effective
and that are also approved by the Food and Drug Administration. The one that has been around
the longest is Orlistat, and it can be found
without prescription under the name Alli. This drug works as an inhibitor
of fat digestion by inhibiting the lipase enzyme. It works to decrease absorption
of fat in the diet. It also induces about
a 5% weight loss. The main complaint
with taking Alli is diarrhea, which some people do not like, and then they stop using
the drug. It is also recommended that
users take a vitamin supplement to reduce the risk
of deficiency, especially since
they do not absorb fat soluble vitamins very well. There have also been
prescription drugs that were approved by the FDA for obesity during the 1980s, ’90s, and early 2000s, but each of these were taken off the market
due to side effects, such as heart disease
and high blood pressure. Between 2010 and 2012, there were no FDA approved medications for obesity. Then, in June 2012,
two drugs were approved, one called Qsymia,
and the other one called Belviq. These drugs do have some side
effects including heart problems and hypertension, and approval
by the FDA was initially denied. However, the FDA subsequently
approved them with warnings and users of the drugs
are supposed to be very closely monitored. Since these drugs are new,
we will have to wait for a few years to see
their benefits as well as their side effects. The last type of treatment for
obesity is bariatric surgery. This is recommended
for individuals who have a BMI greater than 35 kg/m^2 and have
obesity related health problems such as diabetes
or hypertension, or it’s also recommended
for individuals who have a BMI greater than 40 kg/m^2. There are three popular types
of bariatric surgery in the U.S. The adjustable gastric banding and the sleeve gastrectomy procedures make the stomach smaller so individuals feel full after eating a small amount
of food. The Roux-en-Y
gastric bypass procedure makes the stomach
smaller as well, but then it re-routes food
to the latter part of the small intestine
so that not all the calories that are eaten are absorbed. People who have bariatric
surgery learn to avoid eating too much food
and foods high in fat and sugar because they experience gastrointestinal discomfort such as pain, nausea,
and diarrhea. Weight loss following bariatric
surgery averages about 25% and 50-70% of individuals actually maintain
this weight loss. Because of the large amount
of weight loss, change in diet, and change in gut hormones, diabetes and other obesity related diseased are eliminated or reduced in severity
following surgery. However, side effects including
deficiency in iron, vitamin D, calcium, and other essential
nutrients can occur following surgery and can also have severe consequences if not diagnosed and treated. A study by Schauer and others
recently compared two bariatric surgeries
to medical therapy alone using the most definitive
study design, a randomized control trial. This showed that participants
who had bariatric surgery had more dramatic weight loss and remission of diabetes and other health complications, compared to those
who had medical therapy alone. Again, for severely obese people
who have the highest risk of obesity related disease,
bariatric surgery can be an effective treatment. For such an intensive
and costly treatment, though, it is important to ensure
that people who have surgery get the benefits and not
the complications. So, for take home messages,
it’s important to remember that obesity is classified
as a disease, but we are very hopeful
for the future. We know better now
how to prevent obesity and how to treat obesity, especially using
individualized approaches.

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